PROJECT SUMMARY - Contraceptive Discovery, Development and Behavioral Research Center There is a global need for novel contraceptive methods because approximately 40% of pregnancies worldwide are still unintended, about 42 million pregnancies are terminated by abortion, and 830 women per day die of pregnancy-related problems (WHO Nov. 2016). While many contraceptive options exist for women, fewer are available for men. Testosterone-based contraceptives for men have been investigated for over 50 years, but challenges remain for commercialization. For these reasons and to provide couples with additional safe and reversible options for contraception, the development of non-hormonal contraceptives for both men and women is highly desirable to assist with family planning and reduce unintended pregnancies. Another major issue in contraception is inconsistency or lack of compliance with the use of contraceptive methods. The Contraceptive Discovery, Development and Behavioral Research Center will address these current contraceptive challenges in two ways: by discovering and developing non-hormonal male contraceptive agents and finding ways to improve contraceptive use. At team of investigators with interdisciplinary expertise from six Institutions have formed a team to address these issues. They plan to discover selective inhibitors for three validated male non- hormonal contraceptive targets. Project 1 seeks to discover retinoic acid receptor alpha-selective antagonists and the PI is Dr. Debra Wolgemuth from Columbia University. Dr. Jun Qi from the Dana-Farber Cancer Institute is the PI for Project 2: BRDT (testis-specific bromodomain) inhibition. Dr. Pablo Visconti from the University of Massachusetts at Amherst is the PI for Project 3: TSSK6 (testis-specific serine/threonine kinase 6) inhibition. Dr. Jennifer Barber from the University of Michigan is the PI for Project 4: Understanding behavioral patterns in contraceptive use. The Center and its Administrative Core is managed by PI Dr. Gunda Georg from the University of Minnesota, who is also leading the Drug Discovery and Development Core in collaboration with other experts in drug discovery, Drs. Schnbrunn from the Moffitt Cancer Center and Drs. Hawkinson, Walters, and Wong from the University of Minnesota. At the end of the four-year grant period the team expects to have identified lead compounds for each of the three contraceptive development research projects, and these compounds will have been tested in vivo for reversible male contraception for the potential to be developed into preclinical and clinical candidates. For the behavioral research project, we expect to have a better understanding of contraceptive use by couples, which will be informative for tailoring new contraceptive methods for more effective use. Pilot projects be initiated that will generate insights into new contraceptive targets, promote drug discovery and development, and lay the groundwork for contraceptive behavioral research projects. We also expect that early stage investigators, including faculty, graduate students, postdoctoral research associates and visiting scientists will receive mentoring and support in the Center.